Anti-angiogenic effect of high-dose resveratrol in a swine model of metabolic syndrome

Background. Resveratrol has been reported to induce angiogenesis in. ischemia; tissue. We hypothesized that high-dose resveratoral would improve native angiogenesis in a swine model of metabolic syndrome and chronic myocardial ischemia Methods. Yorkshire swine were fed a. normal diet (Control, n = 7), hypercholesterolemic diet (HCD, n = 7), or hypercholesterolemic diet with supplemental resveratrol (100 mg/kg/day orally, HCD-R, it = 7) beginning 1 month prior to surgery. Chronic ischemia was created by placing an. ameroid constrictor on the left curicumflex coronary artery After 7 weeks,,swine underwent functional AM, coronary angiography and serum and head tissue harvest for analysis Results. HCD-R animals had lower body mass in (P < 001), total cholesterol (P < .001), low-density lipoprotein (LDL, P < 001), blood glucose levels (P < .001), and systolic blood pressure (P = .03) than HCD) animals. There was no differente in regional myocardial fiinction at 7 weeks (P = .25). Coronary angiograms revealed no difference in nen pop collateral scores (P = 68) Staining fbr platelet endothelial cell adhesion molecule-I demonshated higher capillary density in the Control group (versus HCD and HCD-R; P = 02). Immunoblotting demonstrated decreased expression of the pro-angiogenic protein macula? endothelial (VE)-cadherin (P = 002) and an increase in anti-angiogenic poteins angiostatin (P = 001) and thrombospondin (P = 02) in the HCD and HCD-R groups Matrix metalloprotease 2 (MMP 2, P = 47) and MMP 9 (P = 12) were not different among pimps. Conclusion. Supplemental resveratrol positively modified cardiovascular risk factors including body mass index, cholesterol, glucose tolerance, and systolic blood pressure. However; it did not increase native collateral formation In the ischemia; myocardium This may be a result of increased angiostatin and thiombospondin leading to decreased expression of VE-cadherin and other pro-angiogenic factors (Surgery 2010,148 ; 453-62.)